The characteristics of the CNS temperature controls and their actions in fever and in normothermia are not fully understood, but previous research on this project suggests that understanding of these controls can be advanced, and perhaps clinical benefits can be derived, by study of the role of central Alpha-melanotropin (MSH) in control of fever and by study of dysthermias due to naturally-occurring brains lesions in man. The plan is to use tests in humans as well as push-pull perfusion, peptide assays, and other techniques in rabbits and squirrel monkeys to learn: whether MSH can be used to reduce fever in man, how naturally-occurring changes in central MSH limit fever, and which portion of the MSH molecule contains the antipyretic "message sequence". Related procedures will be used to determine if antipyretic drugs act by increasing central concentrations of MSH, whether immunoneutralization of endogenous central MSH augments fever as would be expected if the peptide has a physiological role in fever control, and the source of central antipyretic peptide released during fever. Research on neurologic patients is designed to evaluate a procedure for differentiating between fevers due to central injury and those of infectious origin and to learn whether the characteristics of 24-hour temperature records can aid diagnosis. A major aim is to collect additional information on dysthermia/neurologic/neuropathologic relations for development of a guide for understanding such relations.